Nonmetric subadult skeletal sexing traits: I. A blind test of the accuracy of eight previously proposed methods using prehistoric known-sex mummies from northern Chile.
While a number of nonmetric sex-related traits have been proposed, the accurate assignment of sex to subadult skeletal materials is generally considered problematic. Eight previously proposed nonmetric traits of the ilia and mandible have been demonstrated by other researchers to be related to the known-sex of subadults, yet there has been relatively little research attempting to evaluate the utility of these traits using independent collections of known-sex subadult skeletal remains. These eight traits include: elevation of the auricular surface, angle of the greater sciatic notch, depth of the greater sciatic notch, the "arch criteria," curvature of the iliac crest, gonial eversion, mandibular protrusion, and mandibular arcade shape. The present study blindly tested these eight nonmetric traits using 85 autopsied prehistoric known-sex mummified subadult remains from northern Chile that range in age between newborn and 15 skeletal years of age. The two primary questions examined for each trait are: (1) are the different character states for each of the eight traits related to known-sex, and (2) which of the eight traits are accurate enough for use in forensic cases? These questions are examined for each trait by both sex and age class so as to uncover potential sex- and age-related strengths and weaknesses for each of the characteristics. The results indicate that all eight of the previously proposed subadult sex-related traits are indeed related to known-sex, but that there is a great deal of variation by both sex and age in terms of the strength of congruent sex-related associations. With the exception of gonial eversion, all of the traits produced statistically significant chi2 values for their associations with known-sex when all subadult remains were considered. However, when all subadults are considered, only four traits demonstrated acceptable levels of accuracy for forensic applications. These traits include the arch criteria (82.3%), angle of the sciatic notch (80.7%), depth of the sciatic notch (79.0%), and mandibular arcade shape (77.6%). For subadults ranging in age from newborn to five skeletal years of age, only depth of the sciatic notch (81.5%) and the arch criteria (81.5%) approach acceptable levels of accuracy for use in forensic cases. The implications of these results are discussed and recommendations for bioarchaeological and forensic applications are made.


The interaction of asbestos and iron in lung tissue revealed by synchrotron-based scanning X-ray microscopy.
Asbestos is a potent carcinogen associated with malignant mesothelioma and lung cancer but its carcinogenic mechanisms are still poorly understood. Asbestos toxicity is ascribed to its particular physico-chemical characteristics, and one of them is the presence of and ability to adsorb iron, which may cause an alteration of iron homeostasis in the tissue. This observational study reports a combination of advanced synchrotron-based X-ray imaging and micro-spectroscopic methods that provide correlative morphological and chemical information for shedding light on iron mobilization features during asbestos permanence in lung tissue. The results show that the processes responsible for the unusual distribution of iron at different stages of interaction with the fibres also involve calcium, phosphorus and magnesium. It has been confirmed that the dominant iron form present in asbestos bodies is ferritin, while the concurrent presence of haematite suggests alteration of iron chemistry during asbestos body permanence.


Identification of cis-regulatory variation influencing protein abundance levels in human plasma.
Proteins are central to almost all cellular processes, and dysregulation of expression and function is associated with a range of disorders. A number of studies in human have recently shown that genetic factors significantly contribute gene expression variation. In contrast, very little is known about the genetic basis of variation in protein abundance in man. Here, we assayed the abundance levels of proteins in plasma from 96 elderly Europeans using a new aptamer-based proteomic technology and performed genome-wide local (cis-) regulatory association analysis to identify protein quantitative trait loci (pQTL). We detected robust cis-associations for 60 proteins at a false discovery rate of 5%. The most highly significant single nucleotide polymorphism detected was rs7021589 (false discovery rate, 2.5 × 10(-12)), mapped within the gene coding sequence of Tenascin C (TNC). Importantly, we identified evidence of cis-regulatory variation for 20 previously disease-associated genes encoding protein, including variants with strong evidence of disease association show significant association with protein abundance levels. These results demonstrate that common genetic variants contribute to the differences in protein abundance levels in human plasma. Identification of pQTLs will significantly enhance our ability to discover and comprehend the biological and functional consequences of loci identified from genome-wide association study of complex traits. This is the first large-scale genetic association study of proteins in plasma measured using a novel, highly multiplexed slow off-rate modified aptamer (SOMAmer) proteomic platform.


Assessment of early onset surface damage from accelerated disinfection protocol.
The objective of this study was to evaluate the extent and potential mechanisms of early onset surface damage from simulated wiping typical of six-months of routine disinfection and to assess the subsequent microbial risk of surfaces damaged by disinfectants. Eight common material surfaces were exposed to three disinfectants and a neutral cleaner (neutral cleaner, quaternary ammonium, hydrogen peroxide, sodium hypochlorite) in accelerated aging tests to simulate a long-term disinfection routine. Materials were also immersed in dilute and concentrated chemical solutions to induce surface damage. Surfaces were chemically and physically characterized to determine extent of surface damage. Bactericidal efficacy testing was performed on the Quat-based disinfectant using a modified version of EPA standard operating procedure MB-25-02. The wiping protocol increased surface roughness for some material surfaces due to mechanical abrasion of the wiping cloth. The increased roughness did not correlate with changes in bactericidal efficacy. Chemical damage was observed for some surface-disinfectant combinations. The greatest observed effects from disinfectant exposure was in changes in wettability or water contact angle. Early onset surface damage was observed in chemical and physical characterization methods. These high-throughput material measurement methods were effective at assessing nanoscale disinfectant-surface compatibility which may go undetected though routine macroscale testing.


A device for noninvasive assessment of vascular impairment risk in the lower extremity.
The repeatability and resolution of the clinical gold standard of vascular assessment, the ankle-brachial index (ABI), was compared to that of a new device that dynamically assesses tissue perfusion during external loading utilizing laser Doppler flowmetry. Eight subjects of varying levels of vascular impairment were tested in successive weeks using two different sites on the subject's posterior calf. These new measures included the perfusion decrease as well as the unloading delay during cyclic loading. Some new dynamic tissue perfusion measures demonstrated comparable levels of reproducibility with the ABI (e.g., 10%-20%). Only the unloading delay showed potentially enhanced resolution over ABI measures. The perfusion decrease showed little resolution, and the remaining parameters exhibited too great variability (25%-90%). The unloading delay associated with the reperfusion response during cyclic loading displayed the greatest combination of reproducibility and differentiation between subject groups of varying levels of vascular impairment. The preliminary results of this pilot study were also used to estimate sample sizes necessary to detect possible significant (P<0.05) differences between subject groups for all measured perfusion parameters. From these calculations, at least 30 subjects are needed for future study in each of the five subject groups.


Direct Identification of Protein-Protein Interactions by Single-Molecule Force Spectroscopy.
Single-molecule force spectroscopy based on atomic force microscopy (AFM-SMFS) has allowed the measurement of the intermolecular forces involved in protein-protein interactions at the molecular level. While intramolecular interactions are routinely identified directly by the use of polyprotein fingerprinting, there is a lack of a general method to directly identify single-molecule intermolecular unbinding events. Here, we have developed an internally controlled strategy to measure protein-protein interactions by AFM-SMFS that allows the direct identification of dissociation force peaks while ensuring single-molecule conditions. Single-molecule identification is assured by polyprotein fingerprinting while the intermolecular interaction is reported by a characteristic increase in contour length released after bond rupture. The latter is due to the exposure to force of a third protein that covalently connects the interacting pair. We demonstrate this strategy with a cohesin-dockerin interaction.


Droplet impact on flowing liquid films with inlet forcing: the splashing regime.
The impact process of droplets falling obliquely on thin flowing films is studied using a high-speed imaging system with a focus on splashing. Frequency-forcing of the flow rate at the inlet is applied in order to form solitary waves prior to droplet impact. The outcomes associated with impact on targeted regions of the waves are examined; these include the capillary wave region preceding the large wave peak, the flat film region, and the wave hump region. The effect of varying the film flow rate, droplet size, and speed on the splashing regime for each of these regions is elucidated. The results are further compared with those associated with uncontrolled flowing films, and with quiescent films. The present work has demonstrated, for the first time, the contribution made by the spatial structure of waves to the outcome of droplet impact on flowing films.


Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease.
Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.


Thymine Photoproducts but not Thymine Dimers Found in Ultraviolet-Irradiated Bacterial Spores.
Bacillus megateriunm spores labeled with tritiated thymidine were irradiated with monochromatic ultraviolet light, and the DNA of the spores was analvzed for thymine-containing, products. No thymine dimers were observed, but three other thymine photoproducts were found. The unknown products of radiation were produced in vitro by irradiation of DNA that had been dried in the, presence of various salts.


Diagnostic approach to interstitial pneumonias in a single centre: report on 88 cases.
Interstitial pneumonias (IP) cover a broad spectrum of diseases. Open lung biopsies reveal histological patterns and suggest possible diagnoses. Complete clinical records are necessary for final diagnoses. Especially idiopathic interstitial pneumonias (IIP) according to the ATS/ERS classification can only be diagnosed under these predictions. The aim of this study was to compare the results of histological evaluations with the final diagnosis after interdisciplinary case evaluation. 88 patients with interstitial pneumonia that underwent open lung biopsies were investigated. Histology and clinical records were available for review. Diagnosis was made in three steps: first on the sole basis of histology, second with clinical information given initially and third, on the basis of an interdisciplinary case evaluation. 63 patients (72%) were diagnosed as idiopathic interstitial pneumonias according to ATS/ERS criteria. Further 10 (11%) cases of hypersensitivity pneumonitis, 7 (8%) Langerhans cell histiocytosis and 8 (9%) interstitial pneumonias of other known causes or associations were detected. Histological patterns alone agreed with the final diagnosis in 67%. In 82% histology and clinical information given to the pathologist could provide correct diagnosis. In the rest of cases, especially in non idiopathic interstitial pneumonias, an interdisciplinary case evaluation was needed. Diagnosis of interstitial pneumonias by open lung biopsies needs sufficient clinical information. Because of the overlap of histological patterns, an interdisciplinary case evaluation that includes at least one clinical expert and one pathologist with excellent expertise and the follow-up of the patients is necessary to find correct diagnosis in all cases. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5031706258025129.


Four-month test-retest reliability of the MMPI-2 with normal male clergy.
This investigation examined the test-retest coefficients and absolute score changes with the Basic, Supplementary, and Content scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Participants were 111 active male clergy who were not receiving mental health services at the time of their participation and who completed the MMPI-2 on two occasions separated by 4 months. A repeated measures multivariate analysis of variance for the three groups of scales revealed nonsignificant changes in mean T scores. In general, the test-retest coefficients obtained were similar to those reported in the MMPI-2 manual by Butcher, Dahlstrom, Graham, Tellegen, and Kaemmer (1989) and by Spiro, Butcher, Levenson, Aldwin, and Bosse (1993). Increases or decreases of 3 to 6 T-score points were observed for the majority of the scales, and instances in which T-score changes exceeded 10 points were observed on every scale. In sum, the test-retest reliability of the majority of MMPI-2 scales, as represented in this nonclinical sample, appears acceptable and compares favorably with the original MMPI.


Activation of Rho GTPases by DOCK exchange factors is mediated by a nucleotide sensor.
Activation of Rho guanosine triphosphatases (GTPases) to the guanine triphosphate (GTP)-bound state is a critical event in their regulation of the cytoskeleton and cell signaling. Members of the DOCK family of guanine nucleotide exchange factors (GEFs) are important activators of Rho GTPases, but the mechanism of activation by their catalytic DHR2 domain is unknown. Through structural analysis of DOCK9-Cdc42 complexes, we identify a nucleotide sensor within the alpha10 helix of the DHR2 domain that contributes to release of guanine diphosphate (GDP) and then to discharge of the activated GTP-bound Cdc42. Magnesium exclusion, a critical factor in promoting GDP release, is mediated by a conserved valine residue within this sensor, whereas binding of GTP-Mg2+ to the nucleotide-free complex results in magnesium-inducing displacement of the sensor to stimulate discharge of Cdc42-GTP. These studies identify an unusual mechanism of GDP release and define the complete GEF catalytic cycle from GDP dissociation followed by GTP binding and discharge of the activated GTPase.


Pattern of developing the performance template.
The pattern of energy expenditure during sustained high-intensity exercise is influenced by several variables. Data from athletic populations suggest that a pre-exercise conceptual model, or template, is a central variable relative to controlling energy expenditure. The aim of this study was to make systematic observations regarding how the performance template develops in fit individuals who have limited specific experience with sustained high-intensity exercise (eg, time trials). The study was conducted in four parts and involved measuring performance (time and power output) during: (A) six 3 km cycle time trials, (B) three 2 km rowing time trials, (C) four 2 km rowing time trials with a training period between trials 2 and 3, and (D) three 10 km cycle time trials. All time trials were self-paced with feedback to the subjects regarding previous performances and momentary pace. In all four series of time trials there was a progressive pattern of improved performance averaging 6% over the first three trials and 10% over six trials. In all studies improvement was associated with increased power output during the early and middle portions of the time trial and a progressively greater terminal rating of perceived exertion. Despite the change in the pattern of energy expenditure, the subjects did not achieve the pattern usually displayed by athletes during comparable events. This study concludes that the pattern of learning the performance template is primarily related to increased confidence that the trial can be completed without unreasonable levels of exertion or injury, but that the process takes more than six trials to be complete.


Enhancing the get healthy information and coaching service for Aboriginal adults: evaluation of the process and impact of the program.
Non-communicable chronic diseases in Australia contribute to approximately 85% of the total burden of disease; this proportion is greater for Aboriginal communities. The Get Healthy Service (GHS) is effective at reducing lifestyle-based chronic disease risk factors among adults and was enhanced to facilitate accessibility and ensure Aboriginal cultural appropriateness. The purpose of this study is to detail how formative research with Aboriginal communities was applied to guide the development and refinement of the GHS and referral pathways; and to assess the reach and impact of the GHS (and the Aboriginal specific program) on the lifestyle risk factors of Aboriginal participants. Formative research included interviews with Aboriginal participants, leaders and community members, healthcare professionals and service providers to examine acceptability of the GHS; and contributed to the redesign of the GHS Aboriginal program. A quantitative analysis employing a pre-post evaluation design examined anthropometric measures, physical activity and fruit and vegetable consumption of Aboriginal participants using descriptive and chi square analyses, t-tests and Wilcoxon signed-rank tests. Whilst feedback from the formative research was positive, Aboriginal people identified areas for service enhancement, including improving program content, delivery and service promotion as well as ensuring culturally appropriate referral pathways. Once these changes were implemented, the proportion of Aboriginal participants increased significantly (3.2 to 6.4%). There were significant improvements across a number of risk factors assessed after six months (average weight loss: 3.3 kg and waist circumference reduction: 6.2 cm) for Aboriginal participants completing the program. Working in partnership with Aboriginal people, Elders, communities and peak bodies to enhance the GHS for Aboriginal people resulted in an enhanced culturally acceptable and tailored program which significantly reduced chronic disease risk factors for Aboriginal participants. Mainstream telephone based services can be modified and enhanced to meet the needs of Aboriginal communities through a process of consultation, community engagement, partnership and governance.


Biomarkers in solid organ transplantation: establishing personalized transplantation medicine.
Technological advances in molecular and in silico research have enabled significant progress towards personalized transplantation medicine. It is now possible to conduct comprehensive biomarker development studies of transplant organ pathologies, correlating genomic, transcriptomic and proteomic information from donor and recipient with clinical and histological phenotypes. Translation of these advances to the clinical setting will allow assessment of an individual patient's risk of allograft damage or accommodation. Transplantation biomarkers are needed for active monitoring of immunosuppression, to reduce patient morbidity, and to improve long-term allograft function and life expectancy. Here, we highlight recent pre- and post-transplantation biomarkers of acute and chronic allograft damage or adaptation, focusing on peripheral blood-based methodologies for non-invasive application. We then critically discuss current findings with respect to their future application in routine clinical transplantation medicine. Complement-system-associated SNPs present potential biomarkers that may be used to indicate the baseline risk for allograft damage prior to transplantation. The detection of antibodies against novel, non-HLA, MICA antigens, and the expression of cytokine genes and proteins and cytotoxicity-related genes have been correlated with allograft damage and are potential post-transplantation biomarkers indicating allograft damage at the molecular level, although these do not have clinical relevance yet. Several multi-gene expression-based biomarker panels have been identified that accurately predicted graft accommodation in liver transplant recipients and may be developed into a predictive biomarker assay.


Experiences with colored predicate-transition nets for specifying and prototyping embedded systems.
Computer systems in today's society require an increasing amount of embedded software and hardware systems. Their application has introduced new problems for the software engineer combined with the complexity of such systems. In particular, the early stages of the software development process are vital for the successful implementation of computer systems. High order Petri nets are introduced and extended as a powerful formalism for the specification and analysis of concurrent systems. A tool called SystemSpecs has been applied that supports rapid system prototyping with such nets. This survey article provides techniques for early systems analysis that can be used as a real time system prototype for customer presentations. Small examples are extracted from industrial applications to indicate how the described techniques can be used. While the major disadvantage of typical net descriptions is their visual complexity that makes them useless for large distributed systems, the paper also describes how to find overly complex structures, and describes selected methods of how to refine such structures.


Surface and Electrical Characterization of Ag/AgCl Pseudo-Reference Electrodes Manufactured with Commercially Available PCB Technologies.
Lab-on-Chip is a technology that could potentially revolutionize medical Point-of-Care diagnostics. Considerable research effort is focused towards innovating production technologies that will make commercial upscaling financially viable. Printed circuit board manufacturing techniques offer several prospects in this field. Here, we present a novel approach to manufacturing Printed Circuit Board (PCB)-based Ag/AgCl reference electrodes, an essential component of biosensors. Our prototypes were characterized both structurally and electrically. Scanning Electron Microscopy (SEM) and X-Ray Photoelectron Spectroscopy (XPS) were employed to evaluate the electrode surface characteristics. Electrical characterization was performed to determine stability and pH dependency. Finally, we demonstrate utilization along with PCB pH sensors, as a step towards a fully integrated PCB platform, comparing performance with discrete commercial reference electrodes.


Reprogramming the immune system using antibodies.
Tolerance induction induced by monoclonal antibodies or co-receptor blockade is robust enough to resist breakdown by adoptive transfer of lymphocytes. Such resistance, the hallmark of dominant tolerance, is mediated by CD4+ regulatory T cells. CD4+CD25+ T cells inhibit lymphopenia-mediated accumulation of T cells in vivo, but caution should be exerted when investigating antigen-specific regulation in replete mice. A number of different deletional and tolerogenic processes following antibody-induced tolerance are discussed in this chapter, including activation-induced cell death, immunosuppressive cytokines, and immunoprivileged sites. The possibility of spreading tolerance to other cells, including parenchymal cells, is also discussed. This chapter emphasizes recent evidence that shows that self-tolerance does not rely on several mechanisms running independently, but rather a continuum of synergistic and overlapping mechanisms.


Secretory expression of thermostable alkaline protease from Bacillus stearothermophilus FI by using native signal peptide and α-factor secretion signal in Pichia pastoris.
The thermostable alkaline protease from Bacillus stearothermophilus F1 has high potential for industrial applications, and attempt to produce the enzyme in yeast for higher yield was undertaken. Secretory expression of F1 protease through yeast system could improve enzyme's capability, thus simplifying the purification steps. Mature and full genes of F1 protease were cloned into Pichia pastoris expression vectors (pGAPZαB and pPICZαB) and transformed into P. pastoris strains (GS115 and SMD1168H) via electroporation method. Recombinant F1 protease under regulation constitutive GAP promoter revealed that the highest expression was achieved after 72 h cultivation. While inducible AOX promoter showed that 0.5% (v/v) methanol was the best to induce expression. It was proven that constitutive expression strategy was better than inducible system. The α-secretion signal from the plasmid demonstrated higher secretory expression level of F1 protease as compared to native Open Reading Frame (ORF) in GS115 strain (GE6GS). Production medium YPTD was found to be the best for F1 protease expression with the highest yield of 4.13 U/mL. The protein was expressed as His-tagged fusion protein with a size about 34 kDa.


Immune cell populations and cytokine production in spleen and mesenteric lymph nodes after laparoscopic surgery versus conventional laparotomy in mice.
There is evidence that open as well as minimally invasive abdominal surgery impair post-operative innate and acquired immune function. To compare the impact of these approaches as well as the one of different peritoneal gas exposures on immune function, we investigated cellular as well as cytokine-based immune parameters in mesenteric lymph nodes and the spleen postoperatively. Mice (n = 26) were randomly assigned to the 4 study groups: (1) sham controls undergoing anesthesia alone, (2) laparotomy, and (3) air, or (4) carbon dioxide pneumoperitoneum. Mice were sacrificed 48 h after the intervention, and their spleens and mesenteric lymph nodes were harvested. Cytokine production (TNF-α, IL-6, IL-10, and IFN-γ), splenic T cell subpopulations (cytotoxic T cells, T helper cells, and regulatory T cells) were analyzed. TNF-α production of splenocytes 16 h after ex vivo lipopolysaccharides (LPS) stimulation was significantly increased in the laparotomy group compared to all other groups. In contrast, TNF-α production of lymph node cells and IL-6 production of splenocytes after ex vivo LPS stimulation did not differ significantly between the groups. The numbers of regulatory T cells (Treg) in the spleen differed between groups. A significant reduction in Treg cell frequency was detected in the CO(2) insufflation group compared to the laparotomy and the air insufflation group. Our findings demonstrate a distinct difference in immune effector functions and cellular composition of the spleen with regard to splenic TNF-α production and increased numbers of Treg cells in the spleen. These findings are in line with a higher peritoneal inflammatory status consequent to peritoneal air rather than CO(2) exposure. Treg turned out to be key modulators of postoperative dysfunction of acquired immunity.


Modeling of the SPR resolution enhancement for conventional and nanoparticle inclusive sensors by using statistical hypothesis testing.
This paper describes a statistical approach that improves the detection accuracy in simulated experimental surface plasmon resonance (SPR) systems operated in a conventional angular readout scheme. Two SPR system have been investigated: a conventional one and a second one, containing absorbing metallic nanoparticles within the sensing layer. The modified Maxwell-Garnett model that optimally describes the experimental literature results was applied to modeling of the nanoparticle-inclusive sensor. Statistical hypothesis testing was then used to determine the limit of detection of the analyte and nanoparticles. Analyte concentrations as low as 1 pM, corresponding to the refractive index change of 4x10(-8) have been detected with optimized metal layers operated close to the nanoparticle absorption maximum. This is about one order of magnitude smaller than the values obtained in conventional SPR systems with nanoparticles and comparable to the phase-sensitive surface plasmon resonance detection.


Navigating Bioethical Waters: Two Pilot Projects in Problem-Based Learning for Future Bioscience and Biotechnology Professionals.
We believe that the professional responsibility of bioscience and biotechnology professionals includes a social responsibility to contribute to the resolution of ethically fraught policy problems generated by their work. It follows that educators have a professional responsibility to prepare future professionals to discharge this responsibility. This essay discusses two pilot projects in ethics pedagogy focused on particularly challenging policy problems, which we call "fractious problems". The projects aimed to advance future professionals' acquisition of "fractious problem navigational" skills, a set of skills designed to enable broad and deep understanding of fractious problems and the design of good policy resolutions for them. A secondary objective was to enhance future professionals' motivation to apply these skills to help their communities resolve these problems. The projects employed "problem based learning" courses to advance these learning objectives. A new assessment instrument, "Skills for Science/Engineering Ethics Test" (SkillSET), was designed and administered to measure the success of the courses in doing so. This essay first discusses the rationale for the pilot projects, and then describes the design of the pilot courses and presents the results of our assessment using SkillSET in the first pilot project and the revised SkillSET 2.0 in the second pilot project. The essay concludes with discussion of observations and results.


Low-dose persistent organic pollutants increased telomere length in peripheral leukocytes of healthy Koreans.
Although shortened telomeres have been found in many cancers, elongated telomere length has been observed as an early response after low-dose treatment with various chemical carcinogens in vitro and animal experiments, suggesting low-dose exposure to carcinogenic chemicals may function as a tumour promoter at the very early stage of carcinogenesis in humans. This cross-sectional study was performed to examine whether low-dose exposure to persistent organic pollutants (POPs), lipophilic xenobiotics that mainly bioaccumulate in adipose tissue, is associated with telomere length of peripheral blood leukocytes in apparently healthy persons. Telomere length was measured using quantitative polymerase chain reaction method in 84 apparently healthy Koreans. Among various POPs, serum concentrations of organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs) and polybrominated diphenylethers were measured. Most OC pesticides and PCBs were positively and significantly associated with telomere length with correlation coefficients from about +0.25 to +0.35. The strongest associations were observed with p,p'-dichlorodiphenyldichloroethylene, PCB99, PCB153, PCB180, PCB183 and PCB187. When we examined adjusted means of telomere length by quintiles of POPs, the steeper increases of telomere length tended to be observed within relatively lower ranges of POPs. Besides serum concentrations of POPs, none of the other variables studied, including age, were associated with telomere length in this study. We found that telomere length was increasing across low doses of exposure to POPs in which the majority of study subjects were found, suggesting that low-dose POPs may act as a tumour promoter in carcinogenesis in humans.


Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis.
Significant differences in both specificity and avidity of anti-DNA antibodies were observed in the sera of groups of patients with active systemic lupus erythematosus glomerulonephritis, active systemic lupus erythematosus without nephritis, and in IgG eluates obtained by DNAase digestion of isolated glomeruli from glomerulonephritic kidneys. With methylated albumin-kieselguhr fractionated 3H-HeLa DNA as a source of native or single-strand DNA antigen in a modified Farr assay, an increased level of antibody to native DNA was associated with active systemic lupus erythematosus, particularly active nephritis. The avidity of antinative DNA estimated from plots of the reciprocals of bound and free antigen according to the Sips distribution formula was significanly lower in active glomerulonephritis sera than in sera from patients with active systemic lupus erythematosus without nephritis. However, antinative DNA of uniformly high avidity was found in the glomerular eluates. Avidity of single-strand DNA antibodies did not differ in the various patient groups. The data stronly supprot a major role for high avidity antinative-DNA in DNA/antiDNA immune complex-induced glomerular injury in systemic lupus erythematosus.


An analysis of relationships among transformational leadership, job satisfaction, organizational commitment and organizational trust in two Turkish hospitals.
The purpose of this study was to investigate the relationships among employee organizational commitment, organizational trust, job satisfaction and employees' perceptions of their immediate supervisors' transformational leadership behaviors in Turkey. First, this study examined the relationships among organizational commitment, organizational trust, job satisfaction and transformational leadership in two Turkish public hospitals. Second, this investigation examined how job satisfaction, organizational trust and transformational leadership affect organizational commitment. Moreover, it was aimed to investigate how organizational commitment, job satisfaction and transformational leadership affect organizational trust. A quantitative, cross-sectional method, self-administered questionnaire was used for this study. Eight hundred four employees from two public hospitals in Turkey were recruited for collecting data. The overall response rate was 38.14%. The measurement instruments of survey were the Job Satisfaction Survey (developed by P. Spector), the Organizational Commitment Questionnaire (developed by J. Meyer and N. Allen), the Organizational Trust Inventory-short form (developed by L. Cummings and P. Bromiley) and the Transformational Leadership Inventory (TLI) (developed by P. M. Podsakoff). Five-point Likert scales were used in these measurement instruments. Correlation test (the Pearson's rank test) was used to examine relationships between variables. Also, multiple regression analysis was used to determine the regressors for organizational commitment and organizational trust. There were significant relationships among overall job satisfaction, overall transformational leadership and organizational trust. Regression analyses showed that organizational trust and two job satisfaction dimensions (contingent rewards and communication) were significant predictors for organizational commitment. It was found that one transformational leadership dimension (articulating a vision), two job satisfaction dimensions (pay and supervision) and two organizational commitment dimensions (affective commitment and normative commitment) were significant regressors for organizational trust. There is a lack of research in the health organizations regarding organizational commitment, organizational trust, job satisfaction and transformational leadership. The investigator of the proposed study intends to add to the literature and intends to prove that the proposed study would be important for healthcare organizations. A number of specific measures should be undertaken to reduce factors that negatively affect organizational commitment, organizational trust and job satisfaction of hospital personnel and to improve transformational leadership behaviors of hospital administrators.


Intramedullary nailing of femoral shaft fractures: current concepts.
Intramedullary nailing is the preferred method for treating fractures of the femoral shaft. The piriformis fossa and greater trochanter are viable starting points for antegrade nailing. Alternatively, retrograde nailing may be performed. Each option has relative advantages, disadvantages, and indications. Patient positioning can affect the relative ease of intramedullary nailing and the incidence of malalignment. The timing of femoral intramedullary nailing as well as the use of reaming must be tailored to each patient to avoid systemic complications. Associated comorbidities, the body habitus, and associated injuries should be considered when determining the starting point, optimal patient positioning for nailing, whether to use reduction aids as well as which to use, and any modifications of standard technique. Intramedullary nailing of diaphyseal femur fractures provides a stable fixation construct that can be applied using indirect reduction techniques. This method yields high union rates and low complication rates when vigilance is maintained during preoperative planning, the surgical procedure, and the postoperative period.


Position of the American Dietetic Association: local support for nutrition integrity in schools.
It is the position of the American Dietetic Association (ADA) that schools and communities have a shared responsibility to provide students with access to high-quality, affordable, nutritious foods and beverages. School-based nutrition services, including the provision of meals through the National School Lunch Program and the School Breakfast Program, are an integral part of the total education program. Strong wellness policies promote environments that enhance nutrition integrity and help students to develop lifelong healthy behaviors. ADA actively supported the 2004 and proposed 2010 Child Nutrition reauthorization which determines school nutrition policy. ADA believes that the Dietary Guidelines for Americans should serve as the foundation for all food and nutrition assistance programs and should apply to all foods and beverages sold or served to students during the school day. Local wellness policies are mandated by federal legislation for all school districts participating in the National School Lunch Program. These policies support nutrition integrity,including a healthy school environment. Nutrition integrity also requires coordinating nutrition education and promotion and funding research on program outcomes. Registered dietitians and dietetic technicians, registered, and other credentialed staff, are essential for nutrition integrity in schools to perform in policy-making, management, education, and community building roles. A healthy school environment can be achieved through adequate funding of school meals programs and through implementation and evaluation of strong local wellness policies.


A Comparison of Health-Related Quality of Life of Women Awaiting Pelvic Organ Prolapse Surgery versus Hip or Knee Replacement.
Pelvic organ prolapse (POP) can significantly decrease the health-related quality of life (HRQOL) of women. In 2005, provincial and territorial wait time benchmarks were set in areas such as hip and knee replacement, but such efforts were lagging for urogynaecological surgeries. This study aimed to compare wait times and HRQOL scores of females awaiting surgery for POP with those of women awaiting hip or knee replacement. This was a prospectively planned study comparing women undergoing surgical repair of POP to women having a hip or knee replacement. All women completed a validated HRQOL questionnaire, the Short Form 36 Health Survey. The date of the decision to operate was recorded and patients were followed up prospectively to determine surgical wait time. Three of four physical health concepts were significantly worse for orthopedic patients compared with urogynaecology patients, including the physical component summary (29.2 vs. 41.5, respectively, P < 0.001). Urogynaecology and orthopedic patients had similar emotional and mental well-being, as demonstrated by similar mental component summaries (41.5 vs. 44.6, respectively, P = 0.09). The mean wait time at our institution for hip or knee replacement was 98 days, which was significantly shorter than the mean wait time of 210 days for POP surgery (P < 0.001). Despite less physical and pain impact, urogynaecology patients showed similar emotional distress and mental impact compared with orthopedic patients based on a validated HRQOL questionnaire. Because urogynaecology patients waited more than twice as long for their surgery, resources should be directed to prioritize and improve the surgical wait time for urogynaecology patients.


Identification of a rhabdomyosarcoma targeting peptide by phage display with sequence similarities to the tumour lymphatic-homing peptide LyP-1.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. To improve existing therapies and broaden the spectrum of cytotoxic agents that can be used in RMS treatment, we performed a phage-display-based screening for peptides that bind specifically to RMS cells. Two peptides binding to RMS and to other tumour cell lines, but not to normal skeletal muscle cells and fibroblasts, were isolated from phage-displayed random peptide libraries. One peptide, named RMS-I (CQQSNRGDRKRC) contained the integrin-binding motif RGD and its binding was blocked by an antibody against alpha(v)beta(3)integrin, which is expressed on the RMS cell line RD. The isolation of RMS-I confirmed the validity of our screening procedure. The second peptide, named RMS-II (CMGNKRSAKRPC), shows sequence similarity to a previously identified peptide with tumour lymphatic specificity, LyP-1. However, RMS-II binds in vivo to RMS xenografts better than LyP-1 and homes to the tumour blood and not to lymphatic vessels. Therefore, RMS-II represents a promising peptide for the development of RMS-specific targeting approaches.


Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury.
Severe spinal cord injury in humans leads to a progressive neuronal dysfunction in the chronic stage of the injury. This dysfunction is characterized by premature exhaustion of muscle activity during assisted locomotion, which is associated with the emergence of abnormal reflex responses. Here, we hypothesize that undirected compensatory plasticity within neural systems caudal to a severe spinal cord injury contributes to the development of neuronal dysfunction in the chronic stage of the injury. We evaluated alterations in functional, electrophysiological and neuromorphological properties of lumbosacral circuitries in adult rats with a staggered thoracic hemisection injury. In the chronic stage of the injury, rats exhibited significant neuronal dysfunction, which was characterized by co-activation of antagonistic muscles, exhaustion of locomotor muscle activity, and deterioration of electrochemically-enabled gait patterns. As observed in humans, neuronal dysfunction was associated with the emergence of abnormal, long-latency reflex responses in leg muscles. Analyses of circuit, fibre and synapse density in segments caudal to the spinal cord injury revealed an extensive, lamina-specific remodelling of neuronal networks in response to the interruption of supraspinal input. These plastic changes restored a near-normal level of synaptic input within denervated spinal segments in the chronic stage of injury. Syndromic analysis uncovered significant correlations between the development of neuronal dysfunction, emergence of abnormal reflexes, and anatomical remodelling of lumbosacral circuitries. Together, these results suggest that spinal neurons deprived of supraspinal input strive to re-establish their synaptic environment. However, this undirected compensatory plasticity forms aberrant neuronal circuits, which may engage inappropriate combinations of sensorimotor networks during gait execution.


Ombudsman in a mental health centre.
The Israeli Ministry of Health attributes significance to the issue of patients' complaints in mental health settings. A Public Petition Commission was established in Lev Hasharon Mental Health Center, Netanya, Israel, in 1997 and includes representatives from the medical, nursing and social work sectors. We examined the ombudsman's activities in Lev Hasharon Mental Health Center - as a representative institution for mental health centres - in an effort to characterize those who sought the services of the ombudsman and the treatment of the petitions. We also evaluated treatment of the complaint across time, the satisfaction of the complainant and the factors that influenced satisfaction. The files of those who sought the services of the ombudsman prior to and during the six-month duration of the study were examined using a predetermined checklist, and those who approached the ombudsman were contacted and asked whether or not they were satisfied with the treatment of their petition/complaint, and what factors influenced their level of satisfaction. Though solutions were found for only 55% of the problems, 88% of the patients reported satisfaction with the treatment of their petitions and complaints. Beyond the resolution of complaints, the office of the ombudsman improves dialogue with patients and their families, continuously improves in-patient care and perhaps reduces future complaints.


Coordinate regulation of the human UDP-glucuronosyltransferase 1A8, 1A9, and 1A10 genes by hepatocyte nuclear factor 1alpha and the caudal-related homeodomain protein 2.
The human UDP-glucuronosyltransferases (UGT) -1A8 and -1A10 are exclusively expressed in extrahepatic tissues and primarily in the gastrointestinal tract, whereas UGT1A9 is expressed mainly in the liver and kidneys. We have demonstrated previously that the UGT1A8 and UGT1A10 genes, in contrast to the UGT1A9 gene, are regulated via an initiator-like element in their proximal promoters. To determine the elements that contribute to the gastrointestinal expression of UGT1A8 and -1A10, we conducted deletion analysis of the UGT1A8, -1A9, and -1A10 promoters in the colon-derived cell line Caco2. DNA elements contributing significantly to UGT1A8, -1A9, and -1A10 promoter activity were found to reside primarily within 140 base pairs of the transcription start site. Within this region, putative binding sites for the intestine-specific transcription factor, caudal-related homeodomain protein 2 (Cdx2), and hepatocyte nuclear factor 1 (HNF1) were identified. Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter. A single base pair difference between the UGT1A8 and -1A10 promoters, three base pairs downstream of the consensus Cdx2 site, contributed to the observed difference in Cdx2 binding and Cdx2-mediated promoter activation of these two promoters. In addition, Cdx2 was shown to cooperate with HNF1alpha to synergistically activate the UGT1A8, -1A9, and -1A10 promoters. These studies provide insight into the mechanisms controlling the extrahepatic expression of the UGT1A8, -1A9, and -1A10 genes.


Preliminary Results From the C-Pulse OPTIONS HF European Multicenter Post-Market Study.
BACKGROUND The C-Pulse System is an extra-aortic balloon counterpulsation device. It is used to treat patients with heart failure disease in NYHA functional class III or ambulatory class IV. MATERIAL AND METHODS We present preliminary site-reported 6-month data from 3 centers in Germany as part of the prospective observational post-market OPTIONS HF study. RESULTS Between May 2013 and March 2014, the C-Pulse System was implanted in 8 patients (7 male) with a mean age of 61.6±9.3 years. Four had ischemic and 4 had non-ischemic cardiomyopathy. No stroke, myocardial infarction, major bleeding, or major infection due to the device were reported. One patient developed non-device-related refractory tachycardia with worsening heart failure 12 h after surgery and underwent left ventricular assist device implantation. Within 6 months of observation, functional status improved from NYHA III to II in 5 patients, and 2 remained in NYHA III. Mean left ventricular ejection fraction increased from 24.3±7.9% to 44.5±4.5% (p<0.0001). Mean Kansas City Cardiomyopathy Questionnaire overall score improved from 28.6±19.1 to 59.1±22.5 (p=0.0183). Six-minute walk test was performed in 6 out of 7 patients at follow-up. The mean distance improved from 252.0±85.1 m to 279.2±87.5 m (p>0.05). One patient was weaned off the device after 6 months of support. CONCLUSIONS The C-Pulse System provides a therapeutic option for patients with moderate-to-severe heart failure and seems to improve quality of life and cardiac function over time.


Fracture healing in mice lacking Pten in osteoblasts: a micro-computed tomography image-based analysis of the mechanical properties of the femur.
In the United States, approximately eight million osseous fractures are reported annually, of which 5-10% fail to create a bony union. Osteoblast-specific deletion of the gene Pten in mice has been found to stimulate bone growth and accelerate fracture healing. Healing rates at four weeks increased in femurs from Pten osteoblast conditional knock-out mice (Pten-CKO) compared to wild-type mice (WT) of the same genetic strain as measured by an increase in mechanical stiffness and failure load in four-point bending tests. Preceding mechanical testing, each femur was imaged using a Skyscan 1172 micro-computed tomography (μCT) scanner (Skyscan, Kontich, Belgium). The present study used µCT image-based analysis to test the hypothesis that the increased femoral fracture force and stiffness in Pten-CKO were due to greater section properties with the same effective material properties as that of the WT. The second moment of area and section modulus were computed in ImageJ 1.46 (National Institutes of Health) and used to predict the effective flexural modulus and the stress at failure for fourteen pairs of intact and callus WT and twelve pairs of intact and callus Pten-CKO femurs. For callus and intact femurs, the failure stress and tissue mineral density of the Pten-CKO and WT were not different; however, the section properties of the Pten-CKO were more than twice as large 28 days post-fracture. It was therefore concluded, when the gene Pten was conditionally knocked-out in osteoblasts, the resulting increased bending stiffness and force to fracture were due to increased section properties.


Frullania knightbridgei, a new liverwort (Frullaniaceae, Marchantiophyta) species from the deep south of Aotearoa-New Zealand based on an integrated evidence-based approach.
Frullania is a large and taxonomically complex genus. A new liverwort species, Frullania knightbridgeisp. nov. from southern New Zealand, is described and illustrated. The new species, and its placement in Frullania subg. Microfrullania, is based on an integrated evidence-based approach derived from morphology, ecology, experimental growth studies of plasticity, as well as sequence data. Diagnostic characters associated with the leaf and lobule cell-wall anatomy, oil bodies, and spore ultra-structure distinguish it from all other New Zealand species of Frullania. A critical comparison is also made between Frullania knightbridgei and morphologically allied species of botanical regions outside the New Zealand region and an artificial key is provided. The new species is similar to some forms of the widespread Australasian species, Frullania rostrata, but has unique characters associated with the lobule and oil bodies. Frullania knightbridgei is remarkably interesting in comparison with the majority of Frullania species, and indeed liverworts in general, in that it is at least partially halotolerant. Maximum parsimony and maximum likelihood analyses of nuclear ribosomal ITS2 and plastidic trnL-trnF sequences from purported related speciesconfirms its independent taxonomic status and corroborates its placement within Frullania subg. Microfrullania.


A prospective evaluation of an interdisciplinary nutrition-rehabilitation program for patients with advanced cancer.
Cancer can affect many dimensions of a patient's life, and in turn, it should be targeted using a multimodal approach. We tested the extent to which an interdisciplinary nutrition-rehabilitation program can improve the well-being of patients with advanced cancer. Between January 10, 2007, and September 29, 2010, 188 patients with advanced cancer enrolled in the 10-12-week program. Body weight, physical function, symptom severity, fatigue dimensions, distress level, coping ability, and overall quality of life were assessed at the start and end of the program. Of the enrolled patients, 70% completed the program. Patients experienced strong improvements in the physical and activity dimensions of fatigue (effect sizes: 0.8-1.1). They also experienced moderate reductions in the severity of weakness, depression, nervousness, shortness of breath, and distress (effect sizes: 0.5-0.7), and moderate improvements in Six Minute Walk Test distance, maximal gait speed, coping ability, and quality of life (effect sizes: 0.5-0.7) Furthermore, 77% of patients either maintained or increased their body weight. Interdisciplinary nutrition-rehabilitation can be advantageous for patients with advanced cancer and should be considered an integrated part of standard palliative care.


Hyperbaric oxygen therapy for radiation myelitis.
Radiation therapy may damage healthy tissues adjacent to tumor. Hyperbaric oxygen therapy (HBO) is useful in treating soft tissue and osteoradionecrosis. In addition, HBO has been recommended to treat radiation-induced myelitis. We used radiation to induce a predictable myelitis in the spinal cords of rats who were randomized into treatment (HBO) and control groups 8 wk after irradiation. Serial neurologic examination showed no benefit or harm as a result of HBO. This small pilot study did not demonstrate any clinically significant benefit of HBO for radiation myelitis in rats.


Accountability metrics and paying for performance in education and health care.
The track record in paying for performance in education is not good; nevertheless, emphasis on accountability and performance has gained momentum in the last 25 years. This emphasis includes systems of merit pay, career ladders, and national board certification. The general failures of these efforts have led some reformers to suggest that teacher pay be directly related to student value-added performance. This suggestion remains controversial but is also the hottest topic in paying for performance in education. Although many similarities exist between education and health care, major differences may make it even harder to install pay-for-performance systems in health than in education. If those systems are to be tried, experiments should begin in a bottom-up fashion at the unit level, rather than being imposed systemwide.


Climate-disease connections: Rift Valley Fever in Kenya.
All known Rift Valley fever(RVF) outbreaks in Kenya from 1950 to 1998 followed periods of abnormally high rainfall. On an interannual scale, periods of above normal rainfall in East Africa are associated with the warm phase of the El Niño/Southern Oscillation (ENSO) phenomenon. Anomalous rainfall floods mosquito-breeding habitats called dambos, which contain transovarially infected mosquito eggs. The eggs hatch Aedes mosquitoes that transmit the RVF virus preferentially to livestock and to humans as well. Analysis of historical data on RVF outbreaks and indicators of ENSO (including Pacific and Indian Ocean sea surface temperatures and the Southern Oscillation Index) indicates that more than three quarters of the RVF outbreaks have occurred during warm ENSO event periods. Mapping of ecological conditions using satellite normalized difference vegetation index (NDVI) data show that areas where outbreaks have occurred during the satellite recording period (1981-1998) show anomalous positive departures in vegetation greenness, an indicator of above-normal precipitation. This is particularly observed in arid areas of East Africa, which are predominantly impacted by this disease. These results indicate a close association between interannual climate variability and RVF outbreaks in Kenya.


Brucella detection in blood: comparison of the BacT/Alert standard aerobic bottle, BacT/Alert FAN aerobic bottle and BacT/Alert enhanced FAN aerobic bottle in simulated blood culture.
The objective of this study was to compare the performances of the standard aerobic bottle (StAe), FAN aerobic (FANAe) and enhanced FAN aerobic (E-FANAe) (the charcoal component of the FANAe was revised recently to improve the feasibility of Gram smear interpretation) blood culture bottles for BacT/Alert system for the detection of Brucella melitensis in simulated blood culture. Triplicate strains of eight clinical isolates of B. melitensis were studied. Each bottle was inoculated with 5 mL of freshly collected human blood at three different targeted bacterial inocula (10(1), 10(2) and 10(3) CFU/bottle). All bottles were monitored for up to 21 days or until they became positive. The results of time to detection (TTD) on the eight B. melitensis samples were as follows: at 10(1) CFU/bottle, the E-FANAe had a mean TTD significantly shorter than the StAe (48 h vs. 56.2 h, P < 0.05); and at 10(3) CFU/bottle, the FANAe and E-FANAe had a mean TTD significantly shorter than the StAe (41.2 h and 40 h vs. 45.6 h, P < 0.05). The reproducibilities (no.of positive signals/no.of all bottles) of three bottle systems were as follows: at 10(1) CFU/bottle, the reproducibilities of StAe, FANAe and E-FANAe were 96, 83 and 58%, respectively. At 10(3) CFU/bottle, the reproducibilities of StAe, FANAe and E-FANAe were 95, 95 and 91%, respectively. Positive results for the presence of bacteria in Gram smears were confirmed in 68% of StAe, 54% of FANAe and 90% of E-FANAe. In case of suspected brucellosis, the combination of one StAe bottle and one E-FANAe bottle seems to provide the highest and fastest recovery of the organism.


Huperzine A exhibits anti-inflammatory and neuroprotective effects in a rat model of transient focal cerebral ischemia.
Huperzine A, a reversible and selective acetylcholinesterase (AChE) inhibitor, has been reported to display neuroprotective properties. The present study investigated the protective effects of huperzine A in a rat model of transient focal cerebral ischemia created by middle cerebral artery occlusion (MCAO). Huperzine A (0.1 mg/kg), administrated intraperitoneally at the onset of occlusion and 6 h later, markedly restored regional cerebral blood flow, reduced infarct size, and decreased neurological deficit score at 24 h after reperfusion. Along with inhibiting AChE activity, huperzine A inhibited nuclear translocation of transcription factor nuclear factor-kappa B, decreased overexpression of proinflammatory factors in both ipsilateral cortex and striatum, and suppressed activation of glial cells in the ischemic penumbra. Neurological deficit and glial cells activation were also reduced by daily administration of huperzine A for 14 days. Mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist, totally abolished the inhibitory effects of huperzine A on ischemia-induced glial cells activation. Meanwhile, mecamylamine partially reversed the infarct size-reducing effects of huperzine A. In conclusion, our results demonstrate that huperzine A exhibits neuroprotective effects against transient focal cerebral ischemia-induced brain injury and suggest that the protection mechanism may involve a cholinergic anti-inflammatory pathway, in which nAChR plays an essential role.


The effect of hydroalcoholic extract of Stachys lavandulifolia vahl on pregnant mice.
Stachys lavandulifolia is commonly used for many health problems including anxiety. A couple of reports indicate that this plant might have an abortifacient effect on pregnant women. Here we examined this effect on pregnant mice. Incremental doses of 0, 50, 100, 150 and 200 mg/kg of the extracts or normal saline (control group) were injected intraperitoneally to the pregnant mice between 7(th) to 12(th) days of pregnancy. On day 16, uterine tubes were resected and absorbed fetuses were counted. Our study showed that the different average of absorbed fetuses between treated and control groups is significant (P < 0.05). S. lavandulifolia changes the activity level of hypothalamus-pituitary gland-gonad axis due to flavonoid compounds. Also, S. lavandulifolia decreases progesterone concentration resulting in a significant difference between treated and control groups (P < 0.05) and gives rise to failure in fetus survival and consequently, abortion. The length and weight of fetuses decreased in treated groups and there was a significant difference between treated and control groups (P < 0.05). Owing to the possible abortive effect of Stachys lavandulifolia, it is highly recommended to use it cautiously during pregnancy.


Expression levels of long non-coding RNAs are prognostic for AML outcome.
Long non-coding RNA (lncRNA) expression has been implicated in a range of molecular mechanisms that are central in cancer. However, lncRNA expression has not yet been comprehensively characterized in acute myeloid leukemia (AML). Here, we assess to what extent lncRNA expression is prognostic of AML patient overall survival (OS) and determine if there are indications of lncRNA-based molecular subtypes of AML. We performed RNA sequencing of 274 intensively treated AML patients in a Swedish cohort and quantified lncRNA expression. Univariate and multivariate time-to-event analysis was applied to determine association between individual lncRNAs with OS. Unsupervised statistical learning was applied to ascertain if lncRNA-based molecular subtypes exist and are prognostic. Thirty-three individual lncRNAs were found to be associated with OS (adjusted p value < 0.05). We established four distinct molecular subtypes based on lncRNA expression using a consensus clustering approach. LncRNA-based subtypes were found to stratify patients into groups with prognostic information (p value < 0.05). Subsequently, lncRNA expression-based subtypes were validated in an independent patient cohort (TCGA-AML). LncRNA subtypes could not be directly explained by any of the recurrent cytogenetic or mutational aberrations, although associations with some of the established genetic and clinical factors were found, including mutations in NPM1, TP53, and FLT3. LncRNA expression-based four subtypes, discovered in this study, are reproducible and can effectively stratify AML patients. LncRNA expression profiling can provide valuable information for improved risk stratification of AML patients.


Tilted bilayer membranes as simple transmission quarter-wave retardation plates.
A tilted bilayer membrane, which consists of two thin films of transparent optically isotropic materials of different refractive indices, can function as a transmission quarter-wave retarder (QWR) at a high angle of incidence. A specific design using a cryolite-Si membrane in the infrared is presented, and its tolerances to small shifts of wavelength, incidence angle, and film thickness errors are discussed. Some designs provide a dual QWR in transmission and reflection. Such devices provide simple linear-to-circular (and circular-to-linear) polarization transformers. Bilayer eighth-wave retarders without diattenuation are also introduced.


Ischial tuberosity apophysitis and avulsion among athletes.
Ischial tuberosity pain in athletes may be caused by several clinical entities, which include acute and old bony or periosteal avulsions and apophysitis. We studied the natural course of these injuries based on our clinical case series of fourteen patients with apophysitis and twenty-one with avulsion of the ischial tuberosity. Only patients with the diagnosis confirmed by X-ray finding were included. The clinical diagnostic criteria by ischial apophysitis consisted of gradually increasing functional and palpatory pain at the ischial tuberosity without any major trauma at the beginning of the symptoms. Typically there was asymmetry on plain radiographs of the ischial tuberosities in apophysitis; the involved apophyseal area became sclerotic, wider than the non-symptomatic apophysis, osteoporotic patches developed and the lower margin of the ischial tuberosity became irregular. The patients with avulsion reported an acute trauma at the beginning of the symptoms and an avulsion fragment was immediately after injury or later seen in plain radiographs. The mean age of the patients with apophysitis (14.1 yrs) was lower than that of the subjects with avulsions (18.9 yrs). Apophysitis of the ischial tuberosity usually healed well without complications. Avulsions often caused more prolonged pain with referral pain to the posterior parts of the thigh which often required operative interventions. A small bony or periosteal avulsion sometimes grew to a pseudotumor calcification. We recommend conservative treatment as the primary treatment modality for both ischial tuberosity apophysitis and avulsion fractures.


De novo assembly and characterization of a maternal and developmental transcriptome for the emerging model crustacean Parhyale hawaiensis.
Arthropods are the most diverse animal phylum, but their genomic resources are relatively few. While the genome of the branchiopod Daphnia pulex is now available, no other large-scale crustacean genomic resources are available for comparison. In particular, genomic resources are lacking for the most tractable laboratory model of crustacean development, the amphipod Parhyale hawaiensis. Insight into shared and divergent characters of crustacean genomes will facilitate interpretation of future developmental, biomedical, and ecological research using crustacean models. To generate a transcriptome enriched for maternally provided and zygotically transcribed developmental genes, we created cDNA from ovaries and embryos of P. hawaiensis. Using 454 pyrosequencing, we sequenced over 1.1 billion bases of this cDNA, and assembled them de novo to create, to our knowledge, the second largest crustacean genomic resource to date. We found an unusually high proportion of C2H2 zinc finger-containing transcripts, as has also been reported for the genome of the pea aphid Acyrthosiphon pisum. Consistent with previous reports, we detected trans-spliced transcripts, but found that they did not noticeably impact transcriptome assembly. Our assembly products yielded 19,067 unique BLAST hits against nr (E-value cutoff e-10). These included over 400 predicted transcripts with significant similarity to D. pulex sequences but not to sequences of any other animal. Annotation of several hundred genes revealed P. hawaiensis homologues of genes involved in development, gametogenesis, and a majority of the members of six major conserved metazoan signaling pathways. The amphipod P. hawaiensis has higher transcript complexity than known insect transcriptomes, and trans-splicing does not appear to be a major contributor to this complexity. We discuss the importance of a reliable comparative genomic framework within which to consider findings from new crustacean models such as D. pulex and P. hawaiensis, as well as the need for development of further substantial crustacean genomic resources.


Hormonal contraceptive use and risk of HIV-1 disease progression.
For HIV-1-infected women, hormonal contraception prevents unintended pregnancy, excess maternal morbidity, and vertical HIV-1 transmission. Hormonal contraceptives are widely used but their effects on HIV-1 disease progression are unclear. In a prospective study among 2269 chronically HIV-1-infected women from seven countries in eastern and southern Africa and with enrollment CD4 cell counts at least 250 cells/μl, we compared rates of HIV-1 disease progression among those using and not using hormonal contraception (i.e. oral or injectable methods). The primary outcome was a composite endpoint of CD4 decline to less than 200 cells/μl, initiation of antiretroviral therapy, or death. Three hundred and seventy-two women experienced HIV-1 disease progression during 3242 years of follow-up (incidence rate = 11.5 events per 100 person-years). Rates of HIV-1 disease progression among women who were currently using and not using hormonal contraception were 8.54 and 12.31 per 100 person-years, respectively (adjusted hazard ratio 0.74, 95% confidence interval 0.56-0.98, P = 0.04). Rates were 8.58 and 8.39 per 100 person-years for the subsets using injectable and oral contraception (adjusted hazard ratio = 0.72, P = 0.04 for injectable users and adjusted hazard ratio = 0.83, P = 0.5 for oral users compared to women not using hormonal contraception). Sensitivity analyses assessing enrollment or cumulative contraceptive use during the study demonstrated risk estimates closer to 1.0 with no evidence for accelerated disease progression. Among African women with chronic HIV-1 infection, use of hormonal contraception was not associated with deleterious consequences for HIV-1 disease progression.


Progressive restriction in fate potential by neural progenitors during cerebral cortical development.
During early stages of cerebral cortical development, progenitor cells in the ventricular zone are multipotent, producing neurons of many layers over successive cell divisions. The laminar fate of their progeny depends on environmental cues to which the cells respond prior to mitosis. By the end of neurogenesis, however, progenitors are lineally committed to producing upper-layer neurons. Here we assess the laminar fate potential of progenitors at a middle stage of cortical development. The progenitors of layer 4 neurons were first transplanted into older brains in which layer 2/3 was being generated. The transplanted neurons adopted a laminar fate appropriate for the new environment (layer 2/3), revealing that layer 4 progenitors are multipotent. Mid-stage progenitors were then transplanted into a younger environment, in which layer 6 neurons were being generated. The transplanted neurons bypassed layer 6, revealing that layer 4 progenitors have a restricted fate potential and are incompetent to respond to environmental cues that trigger layer 6 production. Instead, the transplanted cells migrated to layer 4, the position typical of their origin, and also to layer 5, a position appropriate for neither the host nor the donor environment. Because layer 5 neurogenesis is complete by the stage that progenitors were removed for transplantation, restrictions in laminar fate potential must lag behind the final production of a cortical layer. These results suggest that a combination of intrinsic and environmental cues controls the competence of cortical progenitor cells to produce neurons of different layers.


COX-2-independent effects of celecoxib sensitize lymphoma B cells to TRAIL-mediated apoptosis.
Despite therapeutic advances, non-Hodgkin lymphomas (NHL) remain incurable. They form a group of neoplasms strongly dependent on their inflammatory microenvironment, which plays an important supportive role in tumor B-cell survival and in the resistance to antitumor immune response. New therapies must consider both tumor cells and their surrounding microenvironment Stromal cells, derived from bone marrow or lymph nodes, and B cells from follicular lymphoma patients were cocultured or cultured alone with celecoxib treatment, a nonsteroidal anti-inflammatory drug, and/or TRAIL, a promising cytotoxic molecule for cancer therapy. In this study, we show that follicular lymphoma stromal cells produce large amounts of PGE2. This production is abrogated after celecoxib treatment, targeting the COX-2 isoenzyme involved in PGE2 synthesis. Furthermore, we demonstrate that celecoxib increases apoptosis in NHL B-cell lines and in primary follicular lymphoma B cells cocultured with stromal cells, but independently of the PGE2/COX-2 axis. Finally, celecoxib increases the apoptotic activity of TRAIL. We provide evidence that celecoxib affects proliferation and sensitizes NHL B-cell lines to apoptosis through COX-2-independent effects by slowing down the cell cycle and decreasing the expression of survival proteins, such as Mcl-1. These data suggest new potent strategies for NHL therapy combining drugs targeting both tumor B cells and survival signals provided by the tumor microenvironment.


[Molecular genetic analysis of Leber's hereditary optic neuropathy with the 3460 mutation in Japanese pedigrees].
We have identified a point mutation at nucleotide position 3460 in the ND1 gene of complex I in a Japanese pedigree with Leber's hereditary optic neuropathy by sequencing the ND genes in mitochondrial DNA. None of the 60 healthy Japanese had the 3460 mutation. The proband and his mother also had the 7444 mutation in the COI gene of complex IV and became nearly blind at age 19 with visual acuities of 0.02 OD and 0.04 OS We screened 30 patients with bilateral optic atrophy for the 3460 mutation, and identified one male patient who had the 3460 mutation in heteroplasmic fashion without carrying the 7444 mutation. He lost his sight at age 14 but it recovered to 1.2 OD and 0.7 OS about two years and half after the onset. The difference in final visual acuity between these two patients may reflect the degree of reduction in mitochondrial energy production.


Questionable accountability: MSF and Sphere in 2003.
This article examines the relationship between Médecins Sans Frontières (MSF) and the Sphere Project. Prior to revisiting the concerns MSF had with the project, it looks at factors that give rise to differences between NGOs and cites some reasons for why an organisation such as MSF would not embrace such a project and clarifies some key elements of MSF-style humanitarianism. The author revisits the original concerns and arguments presented by MSF when it decided not to participate beyond assisting with the establishment of technical standards and key indicators for the handbook. This is followed by a critical discussion examining these concerns and counter-criticism with reference to experiences a few years after the inception of Sphere. It concludes with MSF's perceptions and stance regarding Sphere and accountability in 2003.


Consumption of dietary supplements in a liver transplant population.
The extensive use of alternative medicine products, herbal remedies, and vitamins in large doses has reached an all time high in the general public. Some agents are reported and advertised as immune stimulants and may interfere with patients suffering from immune modification, autoimmune diseases, or transplant recipients. In this report, we will present an investigation into the use of herbal remedies and vitamins in our liver transplant population. We performed an investigation using a questionnaire to determine the use of herbal products and vitamins in our liver transplant population. Medical records were reviewed for each liver transplant recipient that admitted to consuming herbal products or vitamins. Information collected included patient demographics, transplant related information, laboratory tests, outcomes, and herbs or vitamin products used. A total of 290 patients completed and returned the questionnaire. We found 156 admitting to taking more than a standard multivitamin and/or an herbal remedy. All patients were treated with steroids for allograft rejection and experienced a recurrence of amino transaminases following the removal of steroids. Further investigation into dietary supplements using a patient questionnaire form revealed that nearly 50% of patients admitted to using vitamins following transplantation, while 19% used herbal remedies combined with vitamins, most admitting to silymarin. One recipient was ingesting colostrum and required admission for the management of allograft rejection, while 5 patients had consumed large amounts of echinacea or CoEnzyme Q-10 and experienced elevations in their transaminases that resolved with discontinuation of the herb. The review also identified 4 patients with primary biliary cirrhosis and with transaminase elevation (mean values of aspartate aminotransferase and alanine aminotransferase levels of 88 and 95, respectively). All recipients were consuming vitamins, in particular high doses of vitamin E (tocopherol), more than 1 gram per day. All of the transplant recipients were instructed to discontinue all vitamin E products and the amino transaminases resolved over the following 30 to 60 days. In conclusion, this information reveals that a significant proportion of our liver transplant recipients consume herbal remedies. The results of this report suggest that transplant teams need to question each recipient about the use of herbal and vitamin remedies and educate them regarding the potential hazards.


Global molecular diversity of Hepatitis E virus in wild boar and domestic pig.
Our study aim was to describe and characterize the global Hepatitis E virus (HEV) molecular and genotype geographical distribution in domestic pig and wild boar, which could facilitate the traceability of human cases. We performed a systematic sequence search for HEVs identified in domestic pig and wild boar from the available data in GenBank. Only sequences with lengths greater than 300 nt were included. For all sequences, the sequence length, host (i.e., domestic pig or wild boar), country of origin, and HEV genotype/subtype were recorded. Genotypes were assigned by the HEVnet typing tool. The genotype distributions were described by country and host. In countries with sequences available for both species, the genotype coincidences between both animal populations were analyzed. A total of 1404 viral sequences were included: 32.6% from wild boar and 67.4% from domestic pig. Most sequences were consistent with HEV genotype 3 (n = 1165). Genotype 4 was represented by 193 sequences, while genotypes 5 and 6 were represented by only 6 sequences. Sequences were identified in 39 countries, which included all continents except Antarctica. The genotypes with a wide distribution were 3a and 3f. Twenty-five countries had sequences that were found only in domestic pig, three countries only in wild boar, and 11 countries had sequences in both populations. In all countries with available sequences in both populations, the same viral genotype was identified. Our study shows that the number of swine HEV sequences is small, which limits direct comparisons with the sequences identified in humans. The global distribution of genotype 3, together with the wide distribution of genotype 4 in Asia, strongly limits the interpretation of the molecular analysis in the absence of an epidemiological survey of the cases. Increased HEV sequencing in swine should be a priority.


Efficacy of venetoclax in high risk relapsed mantle cell lymphoma (MCL) - outcomes and mutation profile from venetoclax resistant MCL patients.
Venetoclax is effective in relapsed patients with mantle cell lymphoma (MCL). Mechanisms of resistance to venetoclax in MCL are poorly understood. We describe the clinical outcomes and genomic characteristics of 24 multiply relapsed patients (median of five prior lines of therapy) who received venetoclax-based therapies; 67% had progressed on BTK inhibitors (BTKi) and 54% had blastoid or pleomorphic histology. Median follow up after venetoclax treatment was 17 months. The overall response rate was 50% and complete response (CR) rate was 21%, 16 patients had progressed and 15 died. The median progression free, overall and post venetoclax survival were 8, 13.5 and 7.3 months respectively. Whole-exome sequencing (WES) was performed on samples collected from seven patients (including five pairs; before starting venetoclax and after progression on venetoclax). The SMARCA4 and BCL2 alterations were noted only after progression, while TP53, CDKN2A, KMT2D, CELSR3, CCND1, NOTCH2 and ATM were altered 2-4-fold more frequently after progression. In two patients with serial samples, we demonstrated clonal evolution of novel SMARCA4 and KMT2C/D mutations at progression. Mutation dynamics in venetoclax resistant MCL is demonstrated. Our data indicates that venetoclax resistance in MCL is predominantly associated with non-BCL2 gene mutations. Further studies are ongoing in MCL patients to evaluate the efficacy of venetoclax in combination with other agents and understand the biology of venetoclax resistance in MCL.


Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis.
To evaluate the risks of herpes zoster (HZ) and herpes simplex virus (HSV) infection associated with tofacitinib compared with biologic agents among patients with rheumatoid arthritis (RA). Using health plan data from 2010 to 2014, patients with RA initiating tofacitinib or biologics with no history of HZ or HSV were identified, as were incident cases of HZ or HSV. Crude incidence rates were calculated by drug exposure. Cox proportional hazards models evaluated the adjusted association between tofacitinib and HZ, and a composite outcome of HZ or HSV. A total of 2526 patients initiating tofacitinib were compared with initiations of other biologics: anti-tumour necrosis factor (TNF) (n=42 850), abatacept (n=12 305), rituximab (n=5078) and tocilizumab (n=6967). Patients receiving tofacitinib were somewhat younger (mean age 55 years) versus those on other biologics, and somewhat less likely to use concomitant methotrexate (MTX) (39% vs 43%-56%, depending on drug). Crude incidence of HZ associated with tofacitinib was 3.87/100 patient-years (py). After multivariable adjustment, HZ risk was significantly elevated, HR 2.01 (95% CI 1.40 to 2.88) compared with abatacept. Rates and adjusted HRs for all other RA biologics were comparable with each other and abatacept. Older age, female sex, prednisone >7.5 mg/day, prior outpatient infection and greater number of hospitalisations were also associated with increased HZ risk. Incidence rates for the combined outcome were greatest for tofacitinib (7.61/100 py) and also significantly elevated after adjustment (HR=1.40, 95% CI 1.09 to 1.81). The rate of zoster associated with tofacitinib was approximately double that observed in patients using biologics.


Electrorheological Sensor Encapsulating Microsphere Media for Plague Diagnosis with Rapid Visualization.
Plague is a disease infected by an etiological agent, which is transmitted from fleas to a variety of wildlife rodents. Therefore, rapid diagnosis of plague on-site in the field is important. Polystyrene microspheres (SMs) of 2.2 μm diameter were synthesized by emulsion polymerization to adsorb magnetic nanoparticles (FNs), resulting in core-/shell-structured microspheres that generate a significant contrast in relative permittivities between SMs and FNs. Electrorheological displays (EDs) consisting of two indium tin oxide glasses with spacers were constructed to contain core-/shell-structured SM/FN (SM@FN) solutions for observing their transmittance change. The ED encapsulating dispersed SM@FN solution exhibited an opaque state because light was scattered significantly without the application of an alternating electric field (AEF). In the presence of an AEF, the particle chaining behavior results in enhancement of the transmittance of ED. At a specific frequency, the so-called characteristic frequency (Fc), the transmittance reaches a maximum. Fc could be used as an indicator to mark the shell materials. The antibody of Yersinia pestis (ab-Yp) was coated onto the SM@FN as a biosensing medium. The Fc of ab-Yp-modified microspheres shifted from 200 to 750 kHz with antigen coupling of Y. pestis antigen (ag-Yp). In the absence of fluorescence labeling, the large change in ED transmittance could be visualized during the Y. pestis detection. The limit of detection and the limit of quantification were ∼30 and ∼40 ng/μL, respectively, obtained within 30 s according to the highest transmittance of ED under the AEF at 750 kHz. Y. pestis detection was not affected by Escherichia coli and Staphylococcus aureus significantly. Compared with other common immunoassays, including the secondary immunochemical or enzyme-linked steps, this simple electrorheological sensor with high sensitivity and selectivity could be a candidate for on-site plague diagnosis.


A Survey of Current Prophylactic Treatment for Ophthalmia Neonatorum in Croatia and a Review of International Preventive Practices.
BACKGROUND Ophthalmia neonatorum, or neonatal conjunctivitis, is an acute infection that occurs within the first 28 days of life. This aim of this survey was to evaluate the current methods of preventive treatment for ophthalmia neonatorum in maternity hospitals in Croatia. MATERIAL AND METHODS The annual hospital birth rate in Croatia is approximately 40,000. A clinical survey was undertaken with data collected using questionnaires sent to all 32 maternity hospitals in Croatia. There was a 100% response rate to the questionnaires. RESULTS Preventive treatment for ophthalmia neonatorum was administrated to all newborns in 75% (24/32) of Croatian maternity hospitals. In 45.8% of maternity hospitals, (11/32) these procedures were performed within the first hour after birth. In 54.2% of maternity hospitals (13/32), preventive treatment for ophthalmia neonatorum was administrated to all newborns from one to three hours after birth. The main treatment agent was tobramycin (83.3%). Other topical prophylactic treatments included povidone-iodine (8.3%), erythromycin (4.2%), and silver nitrate (4.2%). In 25% of obstetric units, prophylaxis for ophthalmia neonatorum was not used routinely, but in cases of diagnosed neonatal conjunctivitis, antibiotic treatment with tobramycin was mainly used. CONCLUSIONS A survey of all 32 maternity hospitals in Croatia showed variation in the prevalence of preventive treatment for ophthalmia neonatorum and the methods used. These findings support the need to implement standardized preventive measures that both conform to international clinical guidelines and recognize treatment availability in Croatia, where topical povidone-iodine is currently preferred for the prevention of ophthalmia neonatorum.


Evidence-based measurement: which disability scale for neurologic rehabilitation?
To compare the 10-item Barthel Index (BI), 18-item Functional Independence Measure (FIM), and 30-item Functional Independence Measure + Functional Assessment Measure (FIM+FAM) as measures of disability outcomes for neurologic rehabilitation. A total of 149 inpatients from two rehabilitation units in South England specializing in neurologic disorders were studied. Traditional psychometric methods were used to evaluate and compare acceptability (score distributions), reliability (internal consistency, intrarater reproducibility), validity (concurrent, convergent and discriminant construct), and responsiveness (standardized response mean). All three rating scales satisfied recommended criteria for reliable and valid measurement of disability, and are acceptable and responsive in this study sample. The FIM and FIM+FAM total scales are psychometrically similar measures of global disability. The BI, FIM, and FIM+FAM motor scales are psychometrically similar measures of physical disability. The FIM and FIM+FAM cognitive scales are psychometrically similar measures of physical disability. In the sample studied, the BI, FIM, FIM+FAM have similar measurement properties, when examined using traditional psychometric analyses. Although instruments with more items and item response categories generate more qualitative information about an outcome, they may not improve its measurement. Results highlight the importance of using recognized techniques of scale construction to develop health outcome measures.


Epidemiology, prescribing patterns and resource use associated with overactive bladder in UK primary care.
This study aimed to estimate the incidence and prevalence of overactive bladder (OAB) symptoms in the UK and analyse the use of anticholinergic/antispasmodic medications and other healthcare resources within UK general practice. Patients with a record of urinary frequency, urgency, nocturia, urge incontinence or irritable/unstable bladder between 1987 and 2004 were identified from the General Practice Research Database. Demographic characteristics, referrals, consultations, investigations and prescriptions for medications licensed for use in OAB were identified. Regression analyses were used to identify the factors determining switches between medications, referrals and use of healthcare resources. The overall prevalence of OAB-related symptoms was 3.87 per 1000 persons, with an incidence of 2.79 per 1000 person-years. Among 68,910 patients with OAB symptoms, 19,444 (28.2%) received anticholinergic medication, of whom 14,454 (74.3%) received one drug and 4055 (20.9%) received two medications sequentially. Overall, 59.1% of patients were referred to relevant secondary care specialities, 2.8% underwent urinary tests/investigations in primary care and 0.2% were seen by a continence nurse. Resource use was higher among patients who tried several different medications. In conclusion, this study suggests that OAB may be under-diagnosed in the UK and that current guidelines recommending use of anticholinergic medication, continence nurse consultations and urinary tests/investigations are inadequately followed.


Volumetric growth rates of meningioma and its correlation with histological diagnosis and clinical outcome: a systematic review.
Tumour growth has been used to successfully predict progression-free survival in low-grade glioma. This systematic review sought to establish the evidence base regarding the correlation of volumetric growth rates with histological diagnosis and potential to predict clinical outcome in patients with meningioma. This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Databases were searched for full text English articles analysing volumetric growth rates in patients with a meningioma. Four retrospective cohort studies were accepted, demonstrating limited evidence of significantly different tumour doubling rates and shapes of growth curves between benign and atypical meningiomas. Heterogeneity of patient characteristics and timing of volumetric assessment, both pre- and post-operatively, limited pooled analysis of the data. No studies performed statistical analysis to demonstrate the clinical utility of growth rates in predicting clinical outcome. This systematic review provides limited evidence in support of the use of volumetric growth rates in meningioma to predict histological diagnosis and clinical outcome to guide future monitoring and treatment.


Implications of a functional large ribosomal RNA with only three modified nucleotides.
The sequence and structure of the peptidyl transferase region of large subunit ribosomal RNA is highly conserved and specific modified nucleotides could be important structural or functional elements in the catalytic center responsible for peptide bond formation. In fact, it has not been possible to reconstitute active E coli 50S subunits from in vitro transcripts of 23S rRNA and total 50S proteins. It is significant therefore, that the PET56 gene of yeast encodes an essential ribose methyltransferase that specifically modifies a universally conserved nucleotide, G2270, in the peptidyl transferase center of the mitochondrial large ribosomal RNA (21S). Since the loss of this modification in yeast mitochondrial 21S rRNA severely affects the assembly of 54S subunits, it is likely that the analogous 2'-O-methylguanosine at position 2251 (Gm2251) in E coli 23S rRNA is also required for the assembly of 50S subunits. Gm could be a critical structural determinant for the correct folding of the rRNA, the binding of one or more ribosomal proteins, or the interaction of the rRNA with tRNA. Previous work has shown that the mitochondrial large rRNAs are minimally modified relative to the E coli and eukaryotic cytoplasmic rRNAs. By direct chemical analysis using combined high performance liquid chromatography-mass spectrometry, the modification status of the yeast mitochondrial rRNAs was reexamined, revealing the presence of Gm, Um and pseudouridine (psi) in 21S rRNA. The Um was mapped to nucleotide 2791, which corresponds to the ribose methylated and universally conserved U2552 in E coli 23S rRNA, and the psi has been recently mapped to position 2819, which corresponds to psi 2580 in E coli 23S rRNA. The retention of Um and psi nucleotides in the peptidyl transferase center of the otherwise minimally modified mitochondrial rRNAs suggests that these modifications, like Gm2270, might be essential for ribosome assembly or function or both.


Genetic transformation of the synaptic pattern of a motoneuron class in Caenorhabditis elegans.
Caenorhabditis elegans possesses two classes of inhibitory locomotory neurons, the DD and VD motoneurons (mns), and they form complementary components of a cross-inhibitory neuronal network innervating dorsal and ventral body muscles. The DD and VD mns (collectively called the D mns) share a number of morphological and neurochemical features, and mutations in a number of different genes disrupt both cell types in identical ways; however, the DD and VD mns have different lineal origins and different synaptic patterns. Given the number of phenotypic features shared by the D mns, it was of interest to determine what is responsible for the synaptic patterns that distinguish them. An analysis of the locomotory defect along with a genetic epistasis test suggested that unc-55 mutations alter the function of the VD but not the DD mns. Correlated with the defective locomotory behavior of unc-55 mutants was an alteration in the distribution of varicosities, structures associated with presynaptic elements, on the VD mns. The pattern of varicosities of the unc-55 VD mns resembled that of the wild-type DD mns. Moreover, the selective removal of the DD mns revealed that unc-55 VD mns had adopted a functional role appropriate for the DD mns. Thus, unc-55 appears to be involved in producing the synaptic patterns that distinguish the two D mn classes from one another; when the gene is mutated the VD and DD mns become structurally similar and functionally equivalent.


Understanding the presence of mental fatigue in English academy soccer players.
Research has demonstrated that induced mental fatigue impairs soccer-specific technical, tactical and physical performance in soccer players. The findings are limited by the lack of elite players and low ecological validity of the tasks used to induce mental fatigue, which do not resemble the cognitive demands of soccer. The current study collected survey data from English academy soccer players (n = 256; age groups - U14 - U23), with questions comprising of five themes (descriptors of physical and mental fatigue, travel, education, match-play and fixture congestion). The survey consisted of multiple choice responses, checkboxes and blinded/unblinded (for duration based questions) 0-100 arbitrary unit (AU) slider scales. Listening to music (81.6% of players), using social media (58.3%) and watching videos (34.3%) were the most common pre-match activities. Pre-match subjective mental fatigue was low (18.7±18.8 AU), and most frequently reported at the end of a match (47±26 AU) and remained elevated 24-hours post-match (36±27 AU). Travel (29±24 AU), fixture congestion (44±25 AU) and education (30±26 AU) demonstrated a low to moderate presence of subjective mental fatigue. These findings provide an overview of activities performed by English academy soccer players pre-match, and demonstrate that mental fatigue is experienced as a result of match-play.